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Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl methacrylate membranes in vitro

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  • Artificial Kidney / Dialysis
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Abstract

Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.

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Authors and Affiliations

  1. Laboratory for Immune Response and Regulatory Medicine, Fujita Health University School of Medicine, 1-98 Dengakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    Kazuhiro Moriyama

  2. Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Yu Kato, Daisuke Hasegawa, Yasuyoshi Kurimoto, Takahiro Kawaji, Tomoyuki Nakamura, Naohide Kuriyama, Yasuyo Shimomura & Osamu Nishida

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  1. Kazuhiro Moriyama
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  2. Yu Kato
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  3. Daisuke Hasegawa
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  4. Yasuyoshi Kurimoto
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  5. Takahiro Kawaji
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  6. Tomoyuki Nakamura
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  7. Naohide Kuriyama
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  8. Yasuyo Shimomura
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  9. Osamu Nishida
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Contributions

All authors contributed to study conception and design. KM and ON contributed to the conception and design, drafting of the manuscript, and critical revision for important intellectual content. TK, TN, NK, and YS contributed to the writing of the final version. YK, DH, and YK contributed to the laboratory work, data collection, and analysis. All authors commented on previous versions of the manuscript, read, and approved the final version.

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Correspondence to Kazuhiro Moriyama.

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Conflict of interest

Kazuhiro Moriyama has consulting contracts with Baxter Limited and Toray Industries Inc.. The other authors declare that they have no conflicts of interest.

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This in vitro study did not involve experiments or sampling from human subjects or animals.

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Moriyama, K., Kato, Y., Hasegawa, D. et al. Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl methacrylate membranes in vitro. J Artif Organs 23, 240–246 (2020). https://doi.org/10.1007/s10047-020-01173-0

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  • DOI: https://doi.org/10.1007/s10047-020-01173-0

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